289 ASEPTIC

MENINGITIS

AS A COMPLICATION

SCINTICYSTERNOGRAPHY George

Forster,

M.D.,

Stephen

UTILIZING

OF

“‘INDIUM-DTPA

Sacks, M.D. and Nicholas

Christoff,

M.D.*

SUMMARY

The intrathecal administration of numerous substances has been known to cause arachnoiditic as well as aseptic meningitic reactions. Pleocytosis and increased protein in the CSF are well known findings following administration of air or myelographic dyes. This has also been observed with antibiotics. Even intrathecal steroids (e.g. depo-medrol) have been implicated in aseptic meningitic reactions. Despite the wide variety of causative agents, only a small percentage of patients develop clinical manifestations of aseptic meningitis. Are these reactions then caused by specific auto-immune type responses, or are they directly related to local irritants in each case, or a combination of both factors?

We report a case of aseptic meningitis following the intrathecal administration of IllIndium-DTPA. The cause of this reaction is unknown. However, whereas this finding was not considered uncommon wisth RISA, there have been few cases reported with Indium (ALDERSON and SIEGEL, 1973; RHODES, KAMANETZ and WAGNER, 1974). We feel that it is important that one be aware of this potential complication with lllIndium-DTPA. The use of radiopharmaceuticals lumbar puncture for the evaluation standard neurological investigative active Iodinated

Serum Albumin)

introduced into the subarachnoid space via of cerebrospinal fluid dynamics has become a procedure (DI CHIRO, 1966). RISA (Radiowas the first such material

used, but it has been

abandoned by most departments because of occasional adverse reactions (e.g. aseptic meningitis, arachnoiditis; DETMER and BLACKER, 1965; NICOL, 1967; BARNES and FISH, 1972). The reason for these reactions is unknown, however, the albumin in the RISA is suspected to be the cause (DETMER and BLACKER, 1965; NICOL, 1967). The newer radiopharmaceutical lllIndium-DTPA, being non-protein and therefore presumably less bio-reactive, has largely replaced RISA in scinticysternographic applications. The purpose of this paper is to report a case of aseptic meningitis observed following the use of lllIn-DTPA in the cysternography of a patient with dementia. C‘ASE

REPORT

A 60 year old white female was admitted

to ‘Elmhurst

General

Hospital

on October

* Department of Neurology, Mount Sinai School of Medicine, New York, N.Y., U.S.A. and Neurology Service, City Hospital at Elmhurst. Elmhurst. New York, U.S.A. Clin. Neurol.

Neurosurg.

1975-4

290 31, 1975 because of confusion, disorientation, bizarre behavior. difficulty with gait, poor memory, and urinary incontinence. These symptoms began in 1077 with subtle changes in personality and behavior. By 1974 there was obviou\ mental deterioration. At that time neurologic examinations were undertaken clscwhere. Computed tomography was reported as being most compatible with corti-cal atrophy with normal pressure hydrocephalus being less likely. A tentative diagnosis of senile dementia, i.e., Alzheimer’s disease, was made. The patient remained at home until the acute episode which preceded her admission to out institution where investigation of the cause of her dementia was undertaken again. Examination revealed a conspicuous organic mental syndrome with disoricntation, confusion and inability to perform simple mental tasks (e.g. calculation. spelling and reversals). The gait was shuffling and unsteady with frequent falling. She also displayed mild cog-wheel rigidity and tremor. Hepatosplenomegaly was noted on liver-spleen scan. The remainder of the medical and neurologic~ll examinations were normal. On 25-1 l-1975 a lumbar puncture was performed and one ml of IllIn-DTPA (0.1 rads) was introduced into the subarachnoid space. Scans were performed at 24 and 48 hour periods. After 48 hours dye was noted to be present over the cortex. This finding was inconsistent with Normal Pressure Hydrocephalus. A summary of the CSF findings on this and subsequent taps will be found in Table A. On 26-11-1975 the patient developed a temperature of 100 degrees F. At that time chest X-ray, urinanalysis and blood cultures were negative. On 27-l l-1975 the patient experienced shaking chills and was noted to have a temperature of 102 degrees F. She now complained of headache and on examination was found to have mild nuchal rigidity and a positive Kernig and Brudzinski sign. Lumbar TABLE

A

Summary of CSF findings ~-

Date

Initial pressure

11/25

130 mm H,O

1 l/29

140 mm H,O

1214

140 mm

1219

120 mm

12ll5

190

Protein

Glucose

RBC

76 mg%

60

0

fluid clear colorless

Ill mg%

94 mg”/;;

6

2

ibid clear color yellow xanthochromic

H,O

660 mg%

90 mg%

30

23

H,O

85 mg%

70 mg%

40

4

(lymphs 100%) slight xanthochromia

47 mg%

82 mg%

OCC.

0

minimal xanthochromia

mm H.&I

20 mg %

WBC

Comment

(40 % fymphs 60% POlYSJ fluid markedly xanthochromic

291

puncture at this time revealed a markedly xanthochromic fluid with a protein content of 115 mgo/o in contrast to 20 mgO/o for the original lumbar puncture. The cell count was only 2 white cells and 4 red cells per cubic mm. The patient remained unchanged except for some temporary worsening of the organic mental syndrome. On 4-12-1975 the CSF protein had risen to 660 mgo/o and the white cell count to 23 per mms. By 15-12-1975 the protein was down to 47 mgoio. During the period dating from 25-11 to 15-12 no clinical or laboratory cause for the fever was found. Subsequently, she remained afebrile and returned to her usual state. In an attempt to define the fever the following studies were performed: 5 sets of blood cultures were drawn - one of which grew Staph. Epidermidis, but this was believed to be a contaminant since the remaining cultures were negative; AS0 titers were less than 40 Todd units; VDRL was negative; CBC and urinalysis were normal; liver functions showed only mild elevations; SMA-6 and SMA-12 were normaI except for elevated calcium. DISCUSSION

The cause of the aseptic meningitic reactions following intrathecal administration of radiopharmaceuticals is unknown. COOPER and HARBERT (1973) thought that contamination by bacterial endotoxin was responsible. Other investigations have implicated protein or other chemical substances (BARNES and FISH, 1972). With the introduction of Indium diethylenetriaminepentacetic acid (“‘In-DTPA) a nonprotein radiopharmaceutical, the complications attributed to the protein carrier molecule should be eliminated. However, according to RHODES et al. (1974) eight new cases of aseptic meningitis out of a population of 30 patients have been noted. In these cases a positive febrile response was found in six of the 30 cases studied. Two of the six had headache and stiffness of the neck with mifd pleocytosis of the CSF, and one patient developed shaking chills. The significance of their study was in the institution of limulus testing of the Indium specimens. All radiopharmaceuticals are routinely tested by the standard U.S.P. rabbit test for pyrogen activity (EIBERT, 1972). In their study these researchers found that even when the rabbit test was pyrogen negative in those aliquots of radiopharmaceutical in question, the limulus response was markedly pyrogen positive (RHODES et al, 1974). However, JAYBALAN, WHITE and BLANK (1975) report that in three cases out of seventy that developed aseptic meningitis following Indium administration, the aliquots tested were limuius negative. Supported in part by Neurology Training Grant NS05072. ACKNOWLEDGEMENT

We wish to express our thanks to Dr. Melvin D. Yahr for his assistance in the preparation of this manuscript.

292 REFERENCES p. o. and SIEGEL, B. A. (1973) Adverse reactions following lllIn-DTPA cistcrrrography. J. nucl. Med. 14, 609. IJARNES, B. and FISH, M. (1972) Chemical meningitis as a complication of isotope cistern ography. Neurology (Minneap.) 22, 83. COOPER, J. F. and IIARBERT, J. C. (1973) Bacterial endotoxin as a cause of aseptic meningitis following radionuclide cisternography. J. nucl. Med. 14, 387. DETMER, D. E. and BLACKER, H. M. (1965) A case of aseptic meningitis secondary to intrathecal injection of 131 J-human serum albumin. Neurology (Minneap.) 15, 642. DI CHIRO, G. (1966) Observations on the circulation of the cerebrospinal fluid. Acta radiol. (Stockh.) 5, 988. HIBERT, J., JR. (1972) Pyrogen testing horseshoe crab vs. rabbits. Bull. Parenter Drug Assoc. 26, 253. JAYABALAN, v., WHITE, D. and BLANK, M. (1975) Adverse reactions (aseptic meningitis) from lllIndium DTPA cisternographic examinations. Radiology 115, 403. NICOL, c. F. (1967) A second case of aseptic meningitis following isotope cisternography using 131 l-human serum albumin. Neurology (Minneap.) 17, 199. RHODES, B. A., KAMANETZ, G. s. WAGNER, J. R. (1974) The use of limulus testing to reduce the incidence of adverse reactions to cisternographic agents. Neurology (Minneap.) 24, 810. ALDERSON,

Aseptic meningitis as a complication of scinticysternography utilizing 111Indium-dtpa.

The intrathecal administration of numerous substances has been known to cause arachnoiditic as well as aseptic meningitic reactions. Pleocytosis and i...
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